No abstract

The potential usefulness of shed snake skin as a model membrane for transdermal research was examined. There are similarities between shed snake skin and human stratum corneum in terms of structure, composition, lipid content, water permeability, etc. The permeability of various compounds and the contribution of several functional groups to the permeability were also found to be similar between shed snake skin and human skin. Moreover, the permeability of compounds through shed snake skin was increased by Azone, one of the most extensively studied transdermal penetration enhancers. Considering the similarities between shed snake skin and human skin, ease of storage and handling, and low cost, shed snake skin may offer a good model membrane for transdermal research.

Penetration of various compounds through shed snake skin was measured in vitro to examine the effect of lipophilicity and molecular size of a compound on permeability through this model membrane. The permeabilities were found to be controlled by the lipophilicity and the molecular size of the permeant. The smaller and the more lipophilic the compound, the greater the permeability. Equations have been developed to predict the permeability from the molecular weight and the distribution coefficient of a compound. Further, the lipophilicity of shed snake skin is similar to that of human skin and the response of shed snake skin to the molecular size of a permeant is more similar to human skin than to hairless mouse skin. Considering the similarities between shed snake skin and human stratum corneum in terms of structure, composition, and permeability characteristics, the same considerations may apply to permeability through human stratum corneum.

No abstract

A method was developed to prepare 5′‐deoxy‐5′‐substituted‐ψ‐uridine derivatives 4 from 3′,5′‐O‐(1, 1, 3, 3‐tetraisopropyldisiloxanyl)‐1,3‐dimethyl‐ψ‐uridine 1 via a silyl rearrangement reaction. Nucleophilic displacement of the mesyloxy function of 2′‐O‐mesyl‐1,3‐dimethyl‐ψ‐uridine 7 afforded products with the 2′‐substituent in the “down” ribo configuration 8. X‐Ray crystallographic analysis of the 2′‐chloro derivative 8a firmly established the molecular structure of 8 and provided evidence for neighboring group participation of the 4‐carbonyl function of 7 during the nucleophilic reactions. Treatment of 1,3‐dimethyl‐ψ‐uridine 11 with α‐acetoxyisobutyryl chloride afforded a mixture from which two 2′‐chloro‐2′‐deoxy‐C‐nucleosides were obtained. The major product (33% yield) was identical with 8. The minor product (7% yield) was consequently assigned the arabino nucleoside 14. This is the first direct introduction of a 2′‐substituent in the “up” configuration in a preformed pyrimidine nucleoside.